Abstract 4686: T cell repertoire evolution from the normal lung to invasive lung adenocarcinoma

Background: Our knowledge in early lung carcinogenesis is rudimentary. Atypical adenomatous hyperplasia (AAH) is the only preneoplasia type that has been recognized by histopathology and It has been postulated that AAH can progress to adenocarcinoma in situ (AIS), to minimally invasive adenocarcinoma (MIA), and finally to invasive adenocarcinoma (ADC). However, the definition of these lesions remains controversial due to limited supporting molecular evidence. Carcinogenesis results from accumulation of multiple genetic and epigenetic events, with selection for events conferring phenotypic advantage. Immune surveillance, particularly anti-tumor response from T cells is an important host protection process to inhibit carcinogenesis. However, the T cell repertoire landscape and its evolution during lung carcinogenesis have not been well defined. Methods: We performed T cell receptor (TCR) sequencing on multiple spatially separated regions (2-6 regions per lesion) from 23 AAH, 26 AIS, 54 MIA and 14 ADC lesions and paired histologically normal lung tissues from 52 patients clinically presenting with indeterminate pulmonary nodules. Forty-one patients had multifocal diseases and 23 patients carried more than one type of pathology. Results: Compared to pre-/micro-invasive neoplastic lesions (AAH, AIS, MIA) or invasive ADC, normal lung tissues demonstrated significantly less T cell infiltration (p Citation Format: Runzhe Chen, Junya Fujimoto, Alexandre Reuben, Lisha Ying, Xin Hu, Chi-Wan Chow, Jaime Rodriguez Canales, Wenyong Sun, Jinlin Hu, Edwin R. Parra Cuentas, Carmen Behrens, Chang-Jiun Wu, Latasha Little, Curtis Gumbs, Diana Wiesnoski, Guangchun Han, Won-Chul Lee, Paul Scheet, Humam Kadara, Mara Antonoff, Ara A. Vaporciyan, Stephen Swisher, Jianhua Zhang, John Heymach, Waun Ki Hong, Ignacio Wistuba, Andrew Futreal, Dan Su, Jianjun Zhang. T cell repertoire evolution from the normal lung to invasive lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4686.